The long-term objectives of this project are to understand the mechanisms by which histamine can influence the activity of mammalian central neurons, and thereby influence endocrine function. These objectives are to be attained through the use of electrophysiological and pharmacological investigations on neurons of the rat central nervous system. The preparations to be used include long-term organotypic cultures of neonatal rat hypothalamus, slices of adult rat hypothalamus, as well as the intact rat cerebral cortex in situ. Electrophysiological parameters will be recorded both intracellularly and extracellularly, while drugs will be applied systemically or locally by iontophoresis or pressure. A detailed understanding of the cellular effects of histamine should permit a commensurate increase in knowledge about the behavioral and endocrine consequences of the utilization of drugs with affect histaminergic systems. These include conventional antihistamines, which are nonprescription drugs, as well as cimetidine, one of the most widely prescribed therapeutic agents which antagonizes histamine and is known to alter hormone levels in humans.